ABC50 (aka ABCF1) is a member of the ATP Binding Cassette (ABC) family of proteins. ABC50 was first identified as a Tumor Necrosis Factor α-inducible gene in synoviocytes 1, and then re-discovered as a protein that purifies with the translation initiation factor eIF22. Biochemically, ABC50 stimulates formation of complexes between eIF2, GTP and Met-tRNA, implicating it in translation initiation and control. ABC50 is a unique member of the ABC family in that it lacks transmembrane domains. Recently Paytubi et al. showed that the N-terminal region was responsible for eIF2 binding 3. Binding was found to be regulated by Casein Kinase 2 phosphorylation in this domain. Overexpression of ABC50 into HEK293 cells was not observed to boost protein expression 3.
Econazole (Ec) is an imidazole antifungal that also induces endoplasmic reticulum (ER) stress by promoting ER Ca2+ depletion. Ec's mechanism of action involves both Ca2+ influx blockade and stimulation of ER Ca2+ release 4. The latter effect is mediated by reactive oxygen species (ROS) generation at the mitochondria 5. Some cancer cells are extraordinarily sensitive to Ec 6, 7.
The market for therapeutic proteins is currently on the order of $60 Billion worldwide. The largest component of this market is recombinant monoclonal antibodies but also includes other protein classes such as cytokines, growth factors such as insulin, coagulation factors, vaccine subunits and therapeutic enzymes. The diagnostic market is similarly estimated to be $40 Billion worldwide and a significant fraction of this market employs recombinant proteins including monoclonal antibodies. Finally, recombinant proteins for research purposes also represent a large and growing use for recombinant proteins.
It was recently estimated that about half of the 140 recombinant proteins on the market are produced in mammalian cells 8. Given the requirement for large amounts of protein, particularly in the therapeutic setting, there is clearly a need for optimizing natural and recombinant protein production.